Molecule Information

General Information of the Molecule (ID: Mol00101)

• Name: Ubiquitin-like protein ISG15 (ISG15) ,Homo sapiens
• Synonyms: Interferon-induced 15 kDa protein; Interferon-induced 17 kDa protein; IP17; Ubiquitin cross-reactive protein; hUCRP; G1P2; UCRP
• Molecule Type: Protein
• Gene Name: ISG15
• Gene ID: 9636
• Location: chr1:1001138-1014540[+]
• Sequence:
  MGWDLTVKMLAGNEFQVSLSSSMSVSELKAQITQKIGVHAFQQRLAVHPSGVALQDRVPL
  ASQGLGPGSTVLLVVDKCDEPLSILVRNNKGRSSTYEVRLTQTVAHLKQQVSGLEGVQDD
  LFWLTFEGKPLEDQLPLGEYGLKPLSTVFMNLRLRGGGTEPGGRS
• Function: Ubiquitin-like protein which plays a key role in the innate immune response to viral infection either via its conjugation to a target protein (ISGylation) or via its action as a free or unconjugated protein. ISGylation involves a cascade of enzymatic reactions involving E1, E2, and E3 enzymes which catalyze the conjugation of ISG15 to a lysine residue in the target protein. Its target proteins include IFIT1, MX1/MxA, PPM1B, UBE2L6, UBA7, CHMP5, CHMP2A, CHMP4B and CHMP6. Isgylation of the viral sensor IFIH1/MDA5 promotes IFIH1/MDA5 oligomerization and triggers activation of innate immunity against a range of viruses, including coronaviruses, flaviviruses and picornaviruses. Can also isgylate: EIF2AK2/PKR which results in its activation, DDX58/RIG-I which inhibits its function in antiviral signaling response, EIF4E2 which enhances its cap structure-binding activity and translation-inhibition activity, UBE2N and UBE2E1 which negatively regulates their activity, IRF3 which inhibits its ubiquitination and degradation and FLNB which prevents its ability to interact with the upstream activators of the JNK cascade thereby inhibiting IFNA-induced JNK signaling. Exhibits antiviral activity towards both DNA and RNA viruses, including influenza A, HIV-1 and Ebola virus. Restricts HIV-1 and ebola virus via disruption of viral budding. Inhibits the ubiquitination of HIV-1 Gag and host TSG101 and disrupts their interaction, thereby preventing assembly and release of virions from infected cells. Inhibits Ebola virus budding mediated by the VP40 protein by disrupting ubiquitin ligase activity of NEDD4 and its ability to ubiquitinate VP40. ISGylates influenza A virus NS1 protein which causes a loss of function of the protein and the inhibition of virus replication. The secreted form of ISG15 can: induce natural killer cell proliferation, act as a chemotactic factor for neutrophils and act as a IFN-gamma-inducing cytokine playing an essential role in antimycobacterial immunity. The secreted form acts through the integrin ITGAL/ITGB2 receptor to initiate activation of SRC family tyrosine kinases including LYN, HCK and FGR which leads to secretion of IFNG and IL10; the interaction is mediated by ITGAL.
• Uniprot ID: ISG15_HUMAN
• Ensembl ID: ENSG00000187608
• HGNC ID: HGNC:4053

Kingdom: Metazoa
Phylum: Chordata
Class: Mammalia
Order: Primates
Family: Hominidae
Genus: Homo
Species: Homo sapiens

Type(s) of Resistant Mechanism of This Molecule

  UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Drug

Clinical Trial Drug(s) 1 drug(s) in total

TRAIL

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Hepatocellular carcinoma [1]

• Sensitive Disease: Hepatocellular carcinoma [ICD-11: 2C12.2]
• Sensitive Drug: TRAIL
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• In Vitro Model: Huh-7 cells; Liver; Homo sapiens (Human); CVCL_0336
• In Vitro Model: SMMC7721 cells; Uterus; Homo sapiens (Human); CVCL_0534
• In Vitro Model: HLCZ01 cells; Hepatoma; Homo sapiens (Human); CVCL_1J92
• In Vitro Model: LH86 cells; Hepatoma; Homo sapiens (Human); CVCL_8889
• Experiment for Molecule Alteration: Western blot analysis; RT-qPCR
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: microRNA-138 enhances TRAIL-induced apoptosis through interferon-stimulated gene 15 downregulation in hepatocellular carcinoma cells.

Disease- and Tissue-specific Abundances of This Molecule

ICD Disease Classification 02

Liver cancer [ICD-11: 2C12]

Differential expression of molecule in resistant diseases

• The Studied Tissue: Liver
• The Specified Disease: Liver cancer
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 4.66E-06; Fold-change: 5.21E-01; Z-score: 5.92E-01
• The Expression Level of Disease Section Compare with the Adjacent Tissue: p-value: 1.13E-02; Fold-change: 4.81E-01; Z-score: 3.51E-01
• The Expression Level of Disease Section Compare with the Other Disease Section: p-value: 6.68E-01; Fold-change: -2.41E-01; Z-score: -2.45E-01

References

• Ref 1: MicroRNA-138 enhances TRAIL-induced apoptosis through interferon-stimulated gene 15 downregulation in hepatocellular carcinoma cells. Tumour Biol. 2017 Jun;39(6):1010428317710410. doi: 10.1177/1010428317710410.